Cluster of Leptospirosis Acquired Through River Surfing in Switzerland

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Year: 2015

Cluster of leptospirosis acquired through river surfing in Switzerland

Schreiber, Peter W ; Aceto, Leonardo ; Korach, Raphael ; Marreros, Nelson ; Ryser-Degiorgis, Marie-Pierre ; Günthard, Huldrych F

Abstract: Background: In Switzerland, leptospirosis is still considered as a travel-associated disease. After the surprising diagnosis of leptospirosis in a patient who was initially suspected as having primary human immunodeficiency virus infection, we recognized that acquisition of leptospirosis occurred through recreational activities and we identified additional affected individuals. Methods. Detailed anamnesis, excluding occupational exposure, acquisition abroad, and pet contacts, enabled us to detect the source of infection and identify a cluster of leptospirosis. Convalescent sera testing was performed to confirm Lep- tospira infection. Microscopic agglutination tests were used to determine the infecting serovar. Results. We identified a cluster of leptospirosis in young, previously healthy persons. Acquisition of leptospirosis was traced back to a surfing spot on a river in Switzerland (Reuss, Aargau). Clinical presentation was indistinct. Two of the 3 reported cases required hospitalization, and 1 case even suffered from meningitis. Serologic tests indicated infection with the serovar Grippotyphosa in all cases. With the exception of the case with meningitis, no antibiotics were administered, because leptospirosis was diagnosed after spontaneous resolution of most symptoms. Despite a prolonged period of convalescence in 2 cases, full recovery was achieved. Recent reports on beavers suffering from leptospirosis in this region underline the possible water-borne infection of the 3 cases and raise the question of potential wildlife reservoirs. Conclusions. Insufficient awareness of caregivers, which may be promoted by the missing obligation to reporthuman leptospirosis, combined with the multifaceted presentation of the disease result in significant underdiagnosis. More frequent consideration of leptospirosis as differential diagnosis is inevitable, particularly as veterinary data suggest re-emergence of the disease.

DOI: https://doi.org/10.1093/ofid/ofv102

Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-114686 Journal Article Published Version

The following work is licensed under a Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.

Originally published at: Schreiber, Peter W; Aceto, Leonardo; Korach, Raphael; Marreros, Nelson; Ryser-Degiorgis, Marie-Pierre; Günthard, Huldrych F (2015). Cluster of leptospirosis acquired through river surfing in Switzerland. Open Forum Infectious Diseases, 2(3):ofv102. DOI: https://doi.org/10.1093/ofid/ofv102

2 MAJOR ARTICLE

Cluster of Leptospirosis Acquired Through River Surﬁng in Switzerland

Peter W. Schreiber,1,2 Leonardo Aceto,3 Raphael Korach,4 Nelson Marreros,5 Marie-Pierre Ryser-Degiorgis,5 and Huldrych F. Günthard1,2 1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, 2University of Zurich, Institute of Medical Virology, 3Division of Infectious Diseases, Triemli Hospital Zurich, 4Internal Medicine, Waid City Hospital Zurich, and 5University of Bern, Centre for Fish and Wildlife Health, Vetsuisse Faculty, Switzerland Background. In Switzerland, leptospirosis is still considered as a travel-associated disease. After the surprising Downloaded from diagnosis of leptospirosis in a patient who was initially suspected as having primary human immunodeficiency virus infection, we recognized that acquisition of leptospirosis occurred through recreational activities and we identified additional affected individuals. Methods. Detailed anamnesis, excluding occupational exposure, acquisition abroad, and pet contacts, enabled us to detect the source of infection and identify a cluster of leptospirosis. Convalescent sera testing was performed to http://ofid.oxfordjournals.org/ confirm Leptospira infection. Microscopic agglutination tests were used to determine the infecting serovar. Results. We identified a cluster of leptospirosis in young, previously healthy persons. Acquisition of leptospirosis was traced back to a surfing spot on a river in Switzerland (Reuss, Aargau). Clinical presentation was indistinct. Two of the 3 reported cases required hospitalization, and 1 case even suffered from meningitis. Serologic tests indicated infection with the serovar Grippotyphosa in all cases. With the exception of the case with meningitis, no antibiotics were administered, because leptospirosis was diagnosed after spontaneous resolution of most symptoms. Despite a prolonged period of convalescence in 2 cases, full recovery was achieved. Recent reports on beavers suffering from leptospirosis in this region underline the possible water-borne infection of the 3 cases and raise the question of potential wildlife reservoirs. at Zentralbibliothek on November 25, 2015 Conclusions. Insufficient awareness of caregivers, which may be promoted by the missing obligation to report human leptospirosis, combined with the multifaceted presentation of the disease result in significant underdiagnosis. More frequent consideration of leptospirosis as differential diagnosis is inevitable, particularly as veterinary data suggest re-emergence of the disease. Keywords. Leptospira; leptospirosis; recreational activities; water-borne; zoonosis.

Leptospirosis is considered to be a rare disease in indus- on the verge of emerging in industrialized countries [8– trialized countries [1, 2]. However, leptospires are exis- 11]. We report a cluster of 3 cases with acquisition of tent worldwide [3], and due to changing recreational leptospirosis at the same location during river surﬁng behavior (eg, increasing popularity of adventure racing on a standing wave in Switzerland. [4–7]) and ecological changes (eg, global warming, heavy rainfalls, and ﬂooding), this disease may also be METHODS

Study Participants Received 1 April 2015; accepted 3 July 2015. Leptospirosis was diagnosed in Case 1 and Case 2 dur- Correspondence: Peter W. Schreiber, MD, University Hospital Zurich, Division of ing routine clinical work. Based on detailed patient his- Infectious Diseases and Hospital Epidemiology, Rämistrasse 100, Zurich 8091 ([email protected]). tory of these cases, acquisition of leptospirosis at 1 Open Forum Infectious Diseases surfing spot was suspected. Contact to Case 3 was en- © The Author 2015. Published by Oxford University Press on behalf of the Infectious abled by the prior 2 cases. All described patients provid- DiseasesSocietyofAmerica.ThisisanOpenAccessarticledistributedundertheterms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http:// ed written informed consent before publication. creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work Leptospira-Specific Laboratory Analyses is not altered or transformed in any way, and that the work is properly cited. For fi commercial re-use, please contact [email protected]. All Leptospira-speci cenzymeimmunoassays(EIAs) DOI: 10.1093/ofid/ofv102 were performed with the commercially available kits

Leptospirosis Acquired Through River Surfing • OFID • 1 SERION ELISA classic Leptospira IgG and SERION ELISA (CMV) or Epstein-Barr virus (EBV) infection (CMV IgM and classic Leptospira IgM (virion/serion, Würzburg, Germany) CMV IgG: negative; CMV-polymerase chain reaction (PCR): according to manufacturer’s instructions. Microscopic aggluti- negative; EBV IgM: negative; EBV IgG: positive; EBV-PCR: nation tests (MATs) were done at the Bavarian State Office for negative). Polymerase chain reaction of the CSF was negative Health and Food Safety following standard procedure [3]. forCMV,EBV,herpessimplexvirus1and2,andvaricella- Microscopic agglutination tests included the serovars (sv) zoster virus (VZV). Blood cultures remained without growth. Australis, Autumnalis, Ballum, Bataviae, Bratislava, Canicola, Abdominal ultrasound demonstrated discrete splenomegaly of Copenhageni, Grippotyphosa, Hardjo, Hebdomadis, Javanica, 14 cm and no postrenal cause of renal failure. Icterohaemorrhagiae, Pomona, Pyrogenes, Saxkoebing, Sejroe, Repeated human immunodeficiency virus (HIV) screening and Tarassovi. Each month, Leptospira sv are checked by con- tests performed with Roche COBAS Combo-Screening were trol sera provided by the Royal Tropical Institute of Amsterdam. borderline positive. Symptomatic therapy and intravenous hy- Identical amounts of patient’s serum and live antigen were dration resulted in clinical improvement. The patient left the mixed and incubated at 20 to 30°C and then assessed by dark hospital after 4 days. Because clinical findings and laboratory field microscopy. An agglutination of at least 50% identified in results were considered compatible with a primary HIV infec- dark-field microscopy was found to be positive. Titers of reaction, the patient was referred to the outpatient clinic of the Uni-

tive sera were determined by stepwise dilution starting from versity Hospital Zurich. Downloaded from 1:12.5. A positive threshold of 1:100 was used for all sv. For confirmatory reasons, HIV testing was redone using an Abott Architect Combo-Screening test, HIV-1 plasma RNA- Case 1 PCR, testing for p24-Antigen, and a Western blot. All of A 33-year-old male without relevant prior medical history re- these results turned out to be negative, and the diagnosis of pri- ported sudden onset of malaise, fever, myalgia, and headache. mary HIV infection was discarded. http://ofid.oxfordjournals.org/ After persistence of these symptoms for 4 days, he turned to a During the initial hospital stay, leptospirosis was considered general practitioner. A viral infection was suspected, and symp- and serologic testing was prompted. With a delay of a few days, tomatic treatment with a nonsteroidal anti-inflammatory drug Leptospira EIA reported IgM > 100 U/mL and undetectable IgG (NSAID) was initiated. Due to worsening of symptoms, he vis- (SERION ELISA classic assays). Leptospira MAT remained neg- ited an emergency room of a city hospital on the next day. At ative. Because these results were inconclusive, testing was re- presentation, the patient appeared ill and physical examination peated after 5 weeks. Leptospira infection was confirmed with fi

was unremarkable (in particular, there were neither skin nd- seroconversion (Leptospira IgM 74 U/mL, IgG 19 U/mL) and at Zentralbibliothek on November 25, 2015 ings nor conjunctival suffusions). Laboratory results revealed a MAT titer of 1:1600 for serovar Grippotyphosa, 1:800 for se- slightly elevated transaminase levels (alanine aminotransferase rovar Australis, and 1:400 for serovar Bratislava (Table 1). The 133 U/L [normal range: <50 U/L], aspartate aminotransferase patient reported full recovery without any sequelae. 115 U/L [normal range: <50 U/L]), acute kidney injury (maxi- After detailed anamnesis, occupational risk factors or acqui- mum creatinine 146 µmol/L [normal range: 62–106 µmol/L]), sition abroad were excluded, but river surfing as recreational ac- increased C-reactive protein (maximum 174 mg/L [normal tivity was revealed. During this activity, swallowing of water range: <5.0 mg/L]), slight thrombocytopenia (101 G/L [normal occasionally occurred. In particular, the patient reported fre- range: 150–450 G/L]), and leukopenia (2.7 G/L [normal range: quent surfing, approximately 2 times per week, on a standing 3.6–10.5 G/L]) with lymphopenia (0.5 G/L [normal range: 1.1– wave of a river in Switzerland (Reuss River in Aargau). He 4.5 G/L]). Urine chemistry was noticeable for proteinuria surfed the last time on this river 7 days before onset of symp- of approximately 500 mg/day. Because medical history was toms. This surfing spot turned out to be the most probable in- remarkable for recent meningitis of his spouse, and given the fection source. clinical presentation of headaches associated with slight photophobia, a lumbar puncture was performed after an unremark- Case 2 able cranial computed tomography. Cerebrospinal fluid (CSF) A 32-year-old female—the spouse of Case 1—without any rel- examination showed a normal cell count and no signs of a func- evant previous medical history reported sudden onset of mal- tional disorder of the blood-brain barrier. With respect to non- aise and dizziness followed by fever, myalgia, and severe pathological CSF analysis and absence of meningism in physical headache associated with photophobia and phonophobia (∼2 examination, the differential diagnosis meningitis seemed un- weeks before presentation of Case 1). As symptoms persisted, likely. The patient was hospitalized and symptomatic treatment despite self-initiated therapy with acetaminophen and NSAIDs, was continued. Serologic testing for hepatitis viruses A, B, and C she visited a general practitioner. A viral syndrome was suspect- was negative, with exception of positive results for anti-hepatitis ed, and symptomatic therapy with hydration and analgesia was A immunoglobulin (Ig) G, which resulted from prior vaccina- continued. Several consultations at the general practitioner en- tion. There was no indication of a recent cytomegalovirus sued as symptoms deteriorated, despite successively extended

2 • OFID • Schreiber et al Table 1. Results of Leptospira Serology of Cases 1–3

Serologic Test Case 1 Case 2 Case 3 Leptospira IgMa Initial: >100 U/mL 84 U/mLb Initial: 69 U/mL Convalescent: 74 U/mL Convalescent: 29 U/mL Leptospira IgGa Initial: <10 U/mL >100 U/mL Initial: <10 U/mL Convalescent: 19 U/mL Convalescent: 11 U/mL Leptospira MATc Initial: not reactive for all tested sv sv Grippotyphosa 1:800b Initial: ND convalescent: sv Australis 1:100b Convalescent: sv Grippotyphosa 1:1600 sv Grippotyphosa 1:800 sv Australis 1:800 sv Bratislava 1:400 Leptospira complement fixation Initial: ND 1:120b Initial: ND Convalescent: 1:80 Convalescent: 1:120

Abbreviations: ELISA, enzyme-linked immunosorbent assay; Ig, immunoglobulin; MAT, microscopic agglutination tests; ND, not done; sv, serovars. a SERION ELISA classic assay (virion/serion, Würzburg, Germany). b Serology only performed at second presentation. c MAT was performed for sv Australis, Autumnalis, Ballum, Bataviae, Bratislava, Canicola, Copenhageni, Grippotyphosa, Hardjo, Hebdomadis, Javanica,

Icterohaemorrhagiae, Pomona, Pyrogenes, Saxkoebing, Sejroe, and Tarassovi (dilution of 1:100 used as cutoff for all sv, only titers of reactive sv are reported in Downloaded from Table 1).

analgesic therapy. The patient finally visited an emergency serovar Grippotyphosa (titer 1:800 for serovar Grippotyphosa, room as her headaches became intolerable (6 days after onset 1:100 for serovar Australis). Due to the severity of symptoms, http://ofid.oxfordjournals.org/ ofsymptoms).Shewassubfebrileandappearedillandan- antibiotic therapy with doxycycline was administered. She expe- guished; at clinical examination, meningism was present. Crani- rienced progressive improvement within a few days after initia- al computed tomography identified no intracranial bleeding, no tion of therapy, but overall recovery was slow. sinus venous thrombosis, or mass lesions. Laboratory analysis Similar to Case 1, this patient reported surfing on the same revealed moderately increased C-reactive protein (19 mg/L river twice weekly. She remembered the last exposure to river [normal range: <5.0 mg/L]) and slightly elevated alkaline phos- water 2 days before symptom onset. No occupational exposure –

phatase (132 U/L [normal range: 40 130 U/L]). Transaminases, or contacts with pets existed, and her last stay abroad was more at Zentralbibliothek on November 25, 2015 creatinine, and white blood count (WBC) were within the than 1.5 months before illness. In consideration of the maxi- normal range. Lumbar puncture yielded an elevated cell count mum incubation period of 30 days, acquisition of leptospirosis (196/µL [normal range: <6/µL]) with a predominance of neu- most likely occurred in the identical river where her spouse con- trophils and elevated CSF proteins (0.86 g/L [normal range: tracted the infection. 0.23–0.38 g/L). Empiric therapy with acyclovir and ceftriaxone We discussed with Cases 1 and 2 our suspicion that surfing was initiated. Immediately after application of the first dose of on this certain river was the source of infection. Subsequently, ceftriaxone, redness, swelling, and hyperthermia of the extrem- they asked their peer group of river surfers whether they had ities occurred. Because her anamnesis included a penicillin any symptoms suggestive of leptospirosis and were able to iden- allergy, an allergic reaction to ceftriaxone was suspected and tify at least 1 more affected person (ie, Case 3). steroids and antihistamines were administered once. A viral pathogenesis of the meningitis was favored, and antibiotic ther- Case 3 apy was consequently discontinued. Because adenovirus-PCR, Case 3 is a 34-year-old male who belongs to the peer group of CMV-PCR, herpes simplex-PCR and VZV-PCR turned out to the previously described couple. He reported the onset of illness be negative, acyclovir was also stopped. Blood and liquor cul- approximately 1 month before Case 2. He also had no relevant tures showed no bacterial growth. After 1.5 weeks, the patient medical history. Symptoms started with malaise, arthralgia, left the hospital still requiring analgesic combination therapy fever, and chills. High fever persisted despite regular intake of with metamizole and oxycodone for her headaches. After a pe- acetaminophen. Due to illness, he remained in bed most of riod of clinical improvement lasting ∼1 week, she suffered from the time. After 4 days of illness, he sought medical attention progressive malaise, relapsing headaches, and nausea, necessi- at an emergency room. At presentation, he appeared in a slight- tating again admission to a hospital. Since by this time her part- ly reduced general condition, and his vital parameters were ner was suspected of suffering from leptospirosis, she was also within normal range with exception of a body temperature of tested for Leptospira infection. Leptospira antibodies were 37.9°C. His physical examination was unremarkable. Laborato- detected by EIA (IgM 84 U/mL, IgG > 100 U/mL; SERION ry results revealed a slightly elevated creatinine (110 µmol/L ELISA classic assays), and MAT confirmed infection by the [normal range: 62–106 µmol/L]), mild hyponatremia (133

Leptospirosis Acquired Through River Surfing • OFID • 3 mmol/L [normal range: 135–145 mmol/L]), elevated total bilir- findings. However, this person refused to undergo a detailed in- ubin (61 µmol/L [normal range: <21 µmol/L]), and increased terview and serological testing at our outpatient clinic. C-reactive protein (74 mg/L [normal range: <5.0 mg/L]). Leptospirosis is a worldwide zoonosis. In addition, leptospi- His blood count was remarkable for mild thrombocytopenia rosis is still often considered to be a disease of tropical and sub- (97 G/L [normal range: 150–450 G/L]) and left shift (total tropical regions and to occur generally in resource-limited WBC within the normal range). Because the patient reported settings, but leptospirosis also occurs in resource-rich settings. holidays in Indonesia 3 months earlier, malaria was ruled out Switzerland lacks an adequate surveillance system for this dis- after repeated testing. Blood cultures were negative. Serologic ease because human cases are not subjected to mandatory re- testing for HIV, viral hepatitis, schistosomiasis, amebas, and fil- port for more than 15 years. Data from Europe indicated that ariasis showed no signs of infection. Again, a viral syndrome the highest rates of leptospirosis occur in summer and fall was suspected and symptomatic treatment continued. After 1 [13, 14]. Likewise, all described patients in this study suffered week, symptoms started to wane. Subsequently, the patient suf- from leptospirosis either in summer (Case 2 in September fered from severe headaches associated with phonophobia and 2014, Case 3 in August 2014) or in fall (Case 1 in October photophobia, fever reappeared, and scrotal pain with swelling 2014). This seasonal pattern may reflectthefactthatsurvival was present. This time, symptoms persisted for 1 week and of leptospires depends on warm and humid conditions or that

ended with a gradual weakening of illness. The patient arranged the risk of acquisition grows with increasing human water activ- Downloaded from for an appointment with an Infectious Diseases specialist be- ities during hot summer days. Indeed, mean water temperature, cause he mistrusted the diagnosis of a viral infection. At consul- recorded at an observation station approximately 6 miles down- tation, physical examination was unremarkable, but the patient stream (Mellingen, Switzerland), was higher in these months reported almost full recovery at that time. Differential blood (18.4°C in August 2014, 17.8°C in September 2014, 15.3°C in count, creatinine, transaminases, bilirubin, and C-reactive pro- October 2014) than the annual average (12.7°C) [15]. http://ofid.oxfordjournals.org/ tein were within the normal range. Serologic testing revealed el- Infection of humans occurs via skin lesions, mucous mem- evated Leptospira IgM (69 U/mL) with absence of Leptospira branes, and less frequently via inhalation or ingestion. In our IgG (SERION ELISA classic assays). Leptospirosis was favored, case series, infection may have resulted from swallowing water and because the patient felt healthy again, no treatment was ini- or macerated or abraded skin during surfing [5, 16], but none of tiated. Overall, symptoms lasted for approximately 1 month. the reported cases remembered having had skin lesions. Several Convalescent sera testing verified leptospirosis caused by sero- risk groups due to occupational exposure have been identified

var Grippotyphosa (IgM 29 U/mL, IgG 11 U/mL, MAT 1:800 for leptospirosis, including, for example, farmers, veterinarians, at Zentralbibliothek on November 25, 2015 for serovar Grippotyphosa). butchers, and pet sellers, but there is also increasing evidence Also in this case, no occupational exposure was present. This for recreational exposure [4–7, 17, 18]. For physicians, the asso- patient had been surfing on the suspect river in high frequency ciation between recreational activity and leptospirosis may not (approximately 4 times per week) for approximately 6 weeks be- be well known, which can result in significant underdiagnosis of fore onset of illness. The last exposure to river water was report- leptospirosis. With changes in recreational activities, such as the ed 3 days before appearance of initial symptoms. growing popularity of extreme sports and adventure racing, an increase in risk for acquisition of leptospirosis is imaginable. DISCUSSION This hypothesis is also supported by data from the Netherlands that indicated a high proportion of acquisition of leptospirosis To our knowledge, this case series is the first cluster of leptospi- during recreational activities for both autochthonous and im- rosis associated with surfing on a river in Switzerland. In 2012, a ported infections [19]. The incubation period typically lasts single case of leptospirosis was traced back to the same river and 5–14 days. Given the high frequency of river surfing for all re- even to the identical surfing spot [12]. This 28-year-old male ported cases (2–4 times/week), we were not able to identify the presented with sudden onset of fever, chills, headaches, myalgia, most probable date of acquisition. The severity of the disease and arthralgia; laboratory examinations were remarkable for encompasses asymptomatic disease to fatal fulminant infection signs of inflammation, acute renal failure, and elevated transam- [20]. The clinical course is often biphasic and characterized by inases. In consideration of a bacterial infection, this patient re- an acute phase with fever, headache, myalgia, abdominal pain, ceived antibiotic therapy with cephalosporines, resulting in and an immunogenic phase, which may be associated with se- rapid clinical and laboratory improvement. In this case, MAT vere disease manifestations. Initially, all cases suffered from un- identified an infection with Leptospira serovar Bratislava. It specific malaise, myalgia or arthralgia, and fever, which was seems likely that more undiagnosed persons acquired leptospi- misinterpreted as viral syndrome. Two of the 3 cases displayed rosis through surfing on this river. A 4th case of leptospirosis reworsening of symptoms after a short period of improvement, was suspected, because another surfer mentioned that he had only Case 1 described a continuous deterioration. Meningeal in- also suffered from a prolonged period of compatible clinical volvement presenting as aseptic meningitis (shown in Case 2)

4 • OFID • Schreiber et al has recently been reported at a frequency of 5%, and older data infected by the same serovar and likely at the same infection have documented even higher rates [21, 22]. Consistent with source. Leptospira-specific EIAs are approved for diagnostics, literature, the 2 cases with bimodal presentation experienced but positive results need to be confirmed by MAT. Culture re- reappearance of subfebrile temperatures or fever during the quires specialized culture media, and it is insensitive and time- immunogenic phase. Severe manifestations encompass Weil’s consuming. In addition, culture might remain without growth disease (characterized by icterus, acute renal failure, bleeding due to unspecific media used at first choice; also, in this case disorders), renal failure, leptospirosis-associated pulmonary series, unspecific culture media (containing tryptic soy broth) hemorrhage syndrome, and, rarely, myocarditis [22–25]. Diag- were applied. Clinical and laboratory criteria recommended nosis is complicated by protean symptoms and several difficul- by the World Health Organization for the diagnosis of leptospi- ties of diagnosis. Despite several limitations, MAT is considered rosis are summarized in Figure 1 [28]. Diagnosis of leptospirosis as reference serologic test method [11]. The MAT is limited to requires explicit clinical suspicion of this disease to prompt suf- few expert laboratories because this test requires living lepto- ficient testing. spires. A MAT performed in the early course of leptospirosis The repeated false-positive HIV screening test performed can deliver negative results and may take up to 3–4weeksto with Roche Combo-screening of Case 1 seems remarkable. become reactive [26, 27]. This is compatible with the initial neg- Several conditions have been associated with false-positive

ative MAT in Case 1, which developed reactivity in the conva- results such as pregnancy, autoantibodies, hepatitis, cancer, in- Downloaded from lescent sample. Positive MAT results to multiple sv are likely travenous drug use, and inﬂuenza or rubella vaccination [29– due to frequent cross-reactions between sv [3, 21] (Table 1). 31]. Weber et al [32] reported false-positive results using Nevertheless, the highest titers were recorded for serovar Grip- Roche COBAS fourth-generation HIV screening tests at a rate potyphosa in all 3 cases, thus indicating that all patients were of 0.41%. False-positive results were found at the highest http://ofid.oxfordjournals.org/ at Zentralbibliothek on November 25, 2015

Figure 1. Clinical description and recommended case deﬁnition according to the World Health Organization (WHO). Abbreviations: ELISA, enzyme-linked immunosorbent assay; Ig, immunoglobulin; PCR, polymerase chain reaction.

Leptospirosis Acquired Through River Surfing • OFID • 5 frequency in patients with detectable anti-hepatitis A IgM, (Professor Dr. Hatz, Epidemiology, Biostatistics and Preven- pregnant women, and patients suffering from leukemia [32]. tion Institute), a current research project aims at assessing To avoid the impact of a false-positive result, repeated testing the relevance of human leptospirosis in Switzerland. Swiss using different types of tests and repeated samples for diagnosis hospitals have been contacted to report cases of human lepto- of HIV is mandatory [33]. Our findings suggest that leptospiro- spirosis diagnosed in the last years and the assumed mode of sis might also cause false-positive HIV test results. acquisition. Based on these data, an estimate of human lepto- In case of severe leptospirosis, most physicians will prefer an- spirosis cases will be gathered that should help to evaluate tibiotic treatment because some data showed a decreased dura- trends in human disease. If these data indicated a parallel in- tion of illness with antibiotic therapy [34].In a Cochrane review, crease in human leptospirosis, efforts to change the status of no significant benefit of antibiotic treatment was shown [35]. leptospirosis from a nonnotifiable to a notifiable disease Case 2 reported a redness, hyperthermia, and swelling of the would be reinforced. Our work strongly supports a cross-species distal extremities after application of ceftriaxone. Because her “One Health” approach with further collaborations between medical history was positive for a cutaneous reaction after use human and veterinary medicine. of penicillin, an allergic reaction seemed likely. Alternatively, a Jarisch Herxheimer reaction might have been causative [36]. Acknowledgments

Jarisch Herxheimer reactions are described for all spirochetal Downloaded from We thank the 3 patients for their willingness to participate in this study. infections. Administration of antibiotics causes elimination of Financial support. This study was supported by the “Clinical Research spirochetes associated with an acute inflammatory response Priority Program: Viral Infectious Diseases” of the University of Zurich (to and release of large amounts of cytokines. Because these symp- H. F. G. and P. W. S.). Potential conflicts of interest. All authors: No reported conflicts. toms occurred in the early course of the disease, ongoing lepto- All authors have submitted the ICMJE Form for Disclosure of Potential spiremia seems possible, which fits for the differential diagnosis Conflicts of Interest. http://ofid.oxfordjournals.org/ Jarisch Herxheimer reaction. References

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